In this research, a recently developed monoclonal antibody, Mab 126, reactive with a ganglioside antigen, GD2, on neuroblastoma will be investigated for its potential application to the diagnosis and management of neuroblastoma. Preliminary findings showed that the expression of GD2 antigen appears to be restricted to neurectodermal tumors and tissues and that serum levels of GD2 may serve as a tumor marker for both serological diagnosis and therapeutic monitoring of neuroblastoma. We plan to conduct a prospective, long-term study of patient materials collected from more than 30 member institutions of the Pediatric Oncology Group. We will assess the value of GD2 antigen as detected by Mab 126 in the tissue diagnosis of neuroblastoma and in clinical staging of neuroblastoma. We will test the validity of a serological diagnosis of neuroblastoma and will correlate the serum levels of GD2 at the time of diagnosis with the clinical features and final outcome of neuroblastoma patients to determine their prognostic value. The serum levels of GD2 will be correlated with clinical course to assess the usefulness of circulating GD2 as a tumor marker in monitoring neuroblastoma patients. We will search for the presence of circulating antibody to GD2 and their antigen-antibody complexes in patients with neuroblastoma and determine their clinical relevance. We also plan to examine the effects of Mab 126 and antibody against GD2 found in patients' sera on the growth of culture neuroblastoma cells and their expression of GD2 antigen. These undertakings will delineate the value of Mab 126 in the tissue diagnosis and serological diagnosis, in clinical staging and prognostication, and in therapeutic monitoring of neuroblastoma. It may also provide the first model system in which the interaction between a well-defined tumor-associated antigen and its antibody can be dissected. (2)